Genetic Variant TNFSF4:c.153+6011C>A (chr1-173201013-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003326.5(TNFSF4):c.153+6011C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,210 control chromosomes in the GnomAD database, including 993 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 993 hom., cov: 33)

Consequence

TNFSF4
NM_003326.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.505

Publications

3 publications found

Variant links:

Genes affected

TNFSF4 (HGNC:11934): (TNF superfamily member 4) This gene encodes a cytokine of the tumor necrosis factor (TNF) ligand family. The encoded protein functions in T cell antigen-presenting cell (APC) interactions and mediates adhesion of activated T cells to endothelial cells. Polymorphisms in this gene have been associated with Sjogren's syndrome and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

TNFSF4 Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
myocardial infarction, susceptibility to
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

TNFSF4 links:

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new If you want to explore the variant's impact on the transcript NM_003326.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003326.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	NM_003326.5	MANE Select	c.153+6011C>A		intron	N/A	NP_003317.1	P23510-1
	TNFSF4	NM_001297562.2		c.3+4298C>A		intron	N/A	NP_001284491.1	P23510-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TNFSF4	ENST00000281834.4	TSL:1 MANE Select	c.153+6011C>A	intron	N/A	ENSP00000281834.3	P23510-1
TNFSF4	ENST00000367718.5	TSL:1	c.3+4298C>A	intron	N/A	ENSP00000356691.1	P23510-2
TNFSF4	ENST00000714430.1		c.153+6011C>A	intron	N/A	ENSP00000519699.1	P23510-1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15873

AN:

152092

Hom.:

990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.0709

Gnomad EAS

AF:

0.0698

Gnomad SAS

AF:

0.0517

Gnomad FIN

AF:

0.0596

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0780

Gnomad OTH

AF:

0.0962

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.104

AC:

15893

AN:

152210

Hom.:

993

Cov.:

AF XY:

0.105

AC XY:

7833

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.161

AC:

6697

AN:

41522

American (AMR)

AF:

0.140

AC:

2145

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0709

AC:

246

AN:

3470

East Asian (EAS)

AF:

0.0697

AC:

362

AN:

5190

South Asian (SAS)

AF:

0.0509

AC:

246

AN:

4832

European-Finnish (FIN)

AF:

0.0596

AC:

631

AN:

10592

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0780

AC:

5306

AN:

68000

Other (OTH)

AF:

0.0966

AC:

204

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

743

1486

2228

2971

3714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0714

Hom.:

261

Bravo

AF:

0.112

Asia WGS

AF:

0.0700

AC:

244

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.44

(source)

DANN

Benign

0.24

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over